The American Medical Association reports that undertreatment of pain is a major problem for cancer patients as well as for other disease conditions. Approximately 50-75% of cancer patients have pain that is undertreated, and 25% die in severe unrelieved pain. Noninvasive pain medication delivery systems are ideally suited to improve the quality of life for those who experience chronic pain. Currently available noninvasive systems are slow, variable, or require frequent dosing. The goal of this project is to demonstrate the capability of a novel thermal microporation method to enable rapid infusion of pain medication through the skin. The microporation method is a noninvasive, painless, needless, patch-based system which creates an array of microscopic openings in the stratum corneum that increases the drug flux significantly compared to drugs delivered through intact skin. Four top opioid candidates for microporation delivery will be evaluated with an in vitro drug delivery model system that involves studying freshly harvested hairless mouse skin to determine optimal formulation and microporation delivery parameters. The opioid candidates to be tested in vitro with the thermal microporation method include morphine, hydromorphone, fentanyl, and alfentanil. A small pilot clinical study will also be performed to determine the feasibility of delivering fentanyl with a commercially available transdermal patch in conjunction with the microporation system.